Adenocarcinoma arising from adenomatous or sessile serrated polyps; preventable with screening.
Also known as: colon cancer, rectal cancer, colorectal cancer, CRC
Overview
Malignant neoplasm of the colon or rectum, predominantly adenocarcinoma arising from adenomatous (tubular, tubulovillous, villous) or sessile serrated polyps. Anatomic and biologic differences between right colon, left colon, and rectum influence presentation, treatment, and prognosis.
Epidemiology
Second leading cause of cancer death in the US (~150,000 new cases, ~52,000 deaths annually). 5-year survival ~65% (>90% if localized, ~15% if metastatic). Lifetime risk ~4%. Incidence falling overall due to screening, but rising in adults <50 (early-onset CRC).
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Question 1GastrointestinalMedium
A 45-year-old man undergoes colonoscopy that reveals more than 150 adenomatous polyps carpeting the colon and rectum. His father had colorectal cancer at age 40, and genetic testing confirms an APC gene mutation. Which of the following is the most appropriate management?
AProphylactic total proctocolectomy
BProphylactic total abdominal colectomy
CObservation with daily aspirin
DSegmental colectomy with anastomosis
EAnnual colonoscopy with polypectomy
Reveal answer & full explanation
Correct answer: A — Prophylactic total proctocolectomy
AProphylactic total proctocolectomy✓
BProphylactic total abdominal colectomy
CObservation with daily aspirin
DSegmental colectomy with anastomosis
EAnnual colonoscopy with polypectomy
Why Prophylactic total proctocolectomy is correct
More than 100 colonic adenomas with a confirmed APC mutation and an affected first-degree relative define familial adenomatous polyposis (FAP), an autosomal dominant syndrome
Untreated FAP carries a near-100% lifetime risk of colorectal cancer, often by the fourth decade
Prophylactic surgery, typically performed in the late teens to early 20s, is the definitive intervention; the specific operation — restorative proctocolectomy with ileal pouch-anal anastomosis versus total abdominal colectomy with ileorectal anastomosis — is tailored to rectal polyp burden, and with the rectum carpeted in polyps here, only removal of the entire colon and rectum eliminates the at-risk mucosa
Why the others are wrong
Observation with daily aspirin - chemoprevention (NSAIDs such as sulindac) may modestly reduce polyp burden but does not remove the near-certain cancer risk (false reassurance)
Annual colonoscopy with polypectomy - endoscopic polypectomy cannot keep pace with hundreds of polyps and does not prevent cancer in FAP (right-modality-wrong-disease)
Segmental colectomy with anastomosis - resecting one segment leaves the remaining colon and rectum, which this colonoscopy shows are carpeted with adenomas, at near-certain risk of cancer (partial resection of a whole-organ field defect)
Prophylactic total abdominal colectomy - removes the colon but leaves the rectum in place with an ileorectal anastomosis; it is an accepted FAP operation when rectal polyps are few, but with the rectum carpeted in adenomas here the retained rectal mucosa would remain at high risk of cancer (right-operation-wrong-polyp-burden)
Question 2GastrointestinalEasy
A 50-year-old man undergoes his first screening colonoscopy, during which a single 1.2-cm tubular adenoma without high-grade dysplasia or villous histology is identified and completely resected. The remainder of the examination is normal and the bowel preparation was adequate. Which of the following is the most appropriate interval for surveillance colonoscopy?
A1 year
B5 years
C6 months
D7 years
E3 years
Reveal answer & full explanation
Correct answer: E — 3 years
A1 year
B5 years
C6 months
D7 years
E3 years✓
Why 3 years is correct
A single tubular adenoma 10 mm or larger (here 1.2 cm) is an advanced adenoma, which carries enough metachronous-neoplasia risk to warrant a 3-year surveillance interval per current US Multi-Society Task Force post-polypectomy guidance
Size alone (10 mm or larger) qualifies the lesion as advanced even without villous histology or high-grade dysplasia
Complete resection, an adequate bowel preparation, and an otherwise normal examination support the standard 3-year interval rather than an earlier repeat study
Why the others are wrong
7 years — this is the interval for 1-2 SMALL tubular adenomas (under 10 mm); choosing it overlooks that a 1.2-cm adenoma is advanced by size (premature closure on 'low-risk adenoma')
1 year — reserved for patients with more than 10 adenomas on a single examination; it over-surveils a single completely resected adenoma (anchoring on high-risk findings)
5 years — corresponds to 3-4 small tubular adenomas, not a single advanced adenoma; it misapplies the small-adenoma intervals (confused-with-low-risk)
6 months — a 6-month repeat applies after piecemeal resection of an adenoma 20 mm or larger, to check the site for residual tissue; this 1.2-cm adenoma was completely resected, so the 3-year advanced-adenoma interval applies (confused-with-piecemeal-resection)
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Age — median diagnosis ~67 (but rising in younger adults)
Personal or family history of CRC or adenomatous polyps — one affected first-degree relative roughly doubles risk; a first-degree relative with CRC or advanced adenoma → begin screening at 40, and if that relative was diagnosed <60 or ≥2 first-degree relatives are affected, colonoscopy every 5 yr starting at 40 or 10 yr before the youngest relative's diagnosis, whichever is earlier
Other GI malignancies (small bowel, anal) — Imaging and biopsy
Endometriosis (rectal) — Cyclic rectal bleeding in young women
Diagnostic workup
Diagnostic criteria
Histologic confirmation by colonoscopic biopsy. Staging by AJCC 8th edition TNM: T1 invades submucosa, T2 muscularis propria, T3 through the muscularis propria into pericolorectal fat, T4a visceral peritoneum, T4b adjacent organs; N1 1-3 regional nodes, N2 ≥4. Screening modalities (USPSTF: average-risk adults 45-75): colonoscopy every 10 yr, FIT annually, high-sensitivity gFOBT annually, FIT-DNA (Cologuard) every 1-3 yr, flexible sigmoidoscopy every 5 yr (or every 10 yr plus annual FIT), CT colonography every 5 yr. Any positive non-colonoscopy screening test requires follow-up diagnostic colonoscopy, not a repeat stool test, CT colonography or sigmoidoscopy.
Labs
CBC (microcytic anemia)
BMP, LFTs (liver metastases)
CEA — baseline at diagnosis; surveillance marker (not for screening)
Iron studies
Imaging
Colonoscopy with biopsy — DIAGNOSTIC; tattoo lesion for surgical localization
CT chest/abdomen/pelvis with contrast — staging (M assessment)
Rectal cancer: pelvic MRI (T and N staging), endorectal ultrasound (early T staging)
PET-CT not routine; selected cases for equivocal metastases
Mismatch repair (MMR) or MSI testing on all CRCs — Lynch syndrome screening and immunotherapy candidacy
KRAS, NRAS, BRAF, HER2 testing for metastatic disease to guide therapy
Diagnostic algorithm
Feature
Right-sided CRC
Left-sided CRC
Rectal Cancer
Typical presentation
Iron-deficiency anemia, occult bleeding, weight loss
Change in stool caliber, hematochezia, obstruction
Curative-intent surgery is the cornerstone for non-metastatic disease
Lifestyle and risk factor counseling
Stage 0 (Tis) / Stage I (T1-T2 N0)
Polyp with carcinoma in situ or T1: endoscopic resection with clear margins may suffice if low-risk features
Surgical resection for higher-risk lesions: segmental colectomy for colon; for rectum, low anterior resection with total mesorectal excision (sphincter-preserving) unless the tumor involves the anal sphincter or levators, which requires abdominoperineal resection with permanent colostomy
No adjuvant chemotherapy
Colon cancer Stage II (T3-T4 N0)
Surgical resection with adequate lymphadenectomy (≥12 nodes)
MSI-H Stage II patients generally do NOT benefit from 5-FU monotherapy
Colon cancer Stage III (any T, N+)
Surgical resection
Adjuvant FOLFOX or CAPOX × 3-6 months
IDEA trial: 3 months may be sufficient for low-risk Stage III (T1-3, N1)
Locally advanced rectal cancer (T3-T4 or N+)
Total neoadjuvant therapy (TNT) — induction chemo + chemoradiation OR chemoradiation + consolidation chemo, followed by total mesorectal excision (PRODIGE 23, RAPIDO)
Watch-and-wait approach for complete clinical responders (selective)
If resected upfront without neoadjuvant therapy and pathology shows pT3-T4 or N+: adjuvant fluoropyrimidine-based chemoradiation plus FOLFOX or CAPOX (pelvic radiation is added for local control, unlike colon cancer)
Stage IV (metastatic)
Systemic therapy: FOLFOX, FOLFIRI, FOLFOXIRI ± bevacizumab (anti-VEGF) or anti-EGFR (cetuximab, panitumumab — only for RAS/RAF wild-type left-sided tumors)
Targeted therapy by molecular profile: encorafenib + cetuximab for BRAF V600E; trastuzumab-based for HER2+; pembrolizumab/nivolumab for MSI-H/dMMR
Metastasectomy (liver, lung) for oligometastatic disease — potentially curative
Palliative resection/diversion/stent for obstructing tumors
Complications
Bowel obstruction or perforation
Fistula formation
Anemia, hemorrhage
Metastases — liver (most common), lung, peritoneum, ovary (Krukenberg, although gastric more classic), bone, brain
USPSTF lowered CRC screening start age to 45 in 2021 due to rising early-onset disease.
Iron-deficiency anemia in postmenopausal women and any man requires evaluation for GI bleeding — colonoscopy + EGD.
Streptococcus gallolyticus (S. bovis) bacteremia or endocarditis — colonoscopy is mandatory to exclude colon cancer.
Universal MMR/MSI testing on all CRCs at diagnosis identifies Lynch syndrome AND immunotherapy candidates.
MSI-H/dMMR metastatic CRC responds dramatically to pembrolizumab (KEYNOTE-177).
Anti-EGFR therapy (cetuximab, panitumumab) requires RAS/RAF wild-type AND is most effective in LEFT-sided primaries.
Bevacizumab — contraindicated for 28 days post-surgery (poor wound healing, perforation risk).
Rectal cancer requires pelvic MRI for staging (T and N) — drives neoadjuvant therapy decisions.
Surveillance after curative resection: CEA every 3-6 mo × 5 yr, CT chest/abdomen/pelvis annually × 5 yr, colonoscopy at 1 yr then every 3-5 yr.
Lynch syndrome: start colonoscopy at age 20-25 every 1-2 yr; consider screening for endometrial, ovarian, gastric, urothelial cancers.
Post-polypectomy surveillance (USMSTF 2020): 1-2 tubular adenomas <10 mm → 7-10 yr; 3-4 adenomas <10 mm → 3-5 yr; 5-10 adenomas, any adenoma ≥10 mm, villous histology or high-grade dysplasia → 3 yr; >10 adenomas → 1 yr (consider genetic testing); piecemeal resection of a lesion ≥20 mm → 6 mo; normal colonoscopy → 10 yr. Completely resected high-grade dysplasia does not require colectomy.
FAP (APC mutation, autosomal dominant): hundreds to thousands of adenomas with near-100% CRC risk by middle age. Annual colonoscopy from age 10-12, then prophylactic colectomy, usually in the late teens to 20s — proctocolectomy with ileal pouch-anal anastomosis when the rectum is carpeted with polyps, colectomy with ileorectal anastomosis if the rectum is relatively spared. Segmental resection or endoscopic polypectomy cannot control the risk.
References
USPSTF 2021 — US Preventive Services Task Force. Screening for Colorectal Cancer. JAMA 2021;325:1965-1977
NCCN 2024 — NCCN Guidelines Version 5.2024 — Colon Cancer; Rectal Cancer
ACG 2021 — Shaukat A et al. ACG Clinical Guidelines: Colorectal Cancer Screening 2021. Am J Gastroenterol 2021;116:458-479
KEYNOTE-177 — André T et al. Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer. NEJM 2020;383:2207-2218
USMSTF 2020 — Gupta S, Lieberman D, Anderson JC, et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2020;158(4):1131-1153.e5
USMSTF 2017 — Rex DK, Boland CR, Dominitz JA, et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients From the U.S. Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2017;153(1):307-323
ACG 2015 — Syngal S, Brand RE, Church JM, et al. ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes. Am J Gastroenterol 2015;110(2):223-262
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